New Roles for Canonical Transcription Factors in Repeat Expansion Diseases.
Trends Genet
; 36(2): 81-92, 2020 02.
Article
em En
| MEDLINE
| ID: mdl-31837826
ABSTRACT
The presence of microsatellite repeat expansions within genes is associated with >30 neurological diseases. Of interest, (GGGGCC)>30-repeats within C9orf72 are associated with amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). These expansions can be 100s to 1000s of units long. Thus, it is perplexing how RNA-polymerase II (RNAPII) can successfully transcribe them. Recent investigations focusing on GGGGCC-transcription have identified specific, canonical complexes that may promote RNAPII-transcription at these GC-rich microsatellites the DSIF complex and PAF1C. These complexes may be important for resolving the unique secondary structures formed by GGGGCC-DNA during transcription. Importantly, this process can produce potentially toxic repeat-containing RNA that can encode potentially toxic peptides, impacting neuron function and health. Understanding how transcription of these repeats occurs has implications for therapeutics in multiple diseases.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Transcrição Gênica
/
Expansão das Repetições de DNA
/
Proteína C9orf72
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Trends Genet
Assunto da revista:
GENETICA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos